Catheter system providing step reduction for postconditioning

ABSTRACT

A pre-assembled kit for administering ischemic postconditioning comprising a catheter and a handle having a fluid circuit to control and modulate flow of inflation fluid to and from a balloon wherein the catheter is free from additional assembly and preparation procedures such that it is ready-to-use within a variety of vessel sizes.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-In-Part of U.S. patent applicationSer. No. 12/771,968 filed Apr. 30, 2010, and is a Continuation-In-Partof U.S. patent application Ser. No. 12/771,946, filed Apr. 30, 2010, theentirety of which is hereby incorporated by reference.

FIELD OF THE INVENTION

The invention relates to a catheter having a fluid circuit to controland modulate flow of inflation fluid to and from a balloon disposed at adistal section of the catheter system for reducing the number of stepsand time required to perform postconditioning.

BACKGROUND OF THE INVENTION

When a patient suffers from an ischemic event, the blood supply totissues and organs distal to the blockage or occlusion is significantlydiminished. The resulting deprivation of oxygen increases the risk ofnecrosis of the tissues and organs. Generally, a patient suffering anischemic event is treated by minimally invasive catheterization, such asfor example percutaneous transluminal coronary angioplasty (PCTA). PCTAis employed to dilate the ischemic blockage and to restore the bloodsupply to the tissues and organs. Rapid restoration of blood flow afteran ischemic event minimizes the duration of insufficient oxygenation tothe tissue and organs, and therefore optimizes tissue and organsurvival. However, it has now been found that restoring blood supply ina rapid and consistent manner results in reperfusion injury. A shock tothe tissues and organs from rapid oxygen re-saturation and abruptchanges to pH level in the tissue can results in an overall increase inthe infarct size.

Reperfusion injury results from the rapid opening of a blood vessel suchas those of the coronary, peripheral, and/or cerebral vasculature. Forexample, the rapid opening of an artery of the heart during aST-Elevation Myocardial Infarction (“STEMI”), or an artery to the brain(ischemic stroke), or an artery to the other vital organs such as thekidney or liver or other tissues of the body sometimes causes ischemicinjury in myocardial, cerebral, peripheral and spinal infarction, forexample.

One method to reduce or prevent the occurrence of reperfusion injury isa technique known as postconditioning. Postconditioning is a methodduring which the blood flow in the infarcted artery is stopped andstarted for multiple cycles immediately after re-opening of initial flowfrom the STEMI. This re-opening of flow can be either before or afterangioplasty, with or without placement of a stent. Currently, physicianstypically use an angioplasty catheter to perform postconditioning.However, the use of an angioplasty catheter is not optimal. For example,the angioplasty balloon is not configured to quickly occlude flow.Instead, the angioplasty balloon is designed to carefully create a new,circular lumen. Additionally, the typical angioplasty balloon isnon-compliant, meaning it is designed and/or made of a material that ismeant to be inflated with a range of pressures, while not significantlychanging its outer diameter size. A typical non-compliant angioplastyballoon becomes circular at approximately 4 atmospheres of pressure. Asthe balloon pressure is increased, the outer diameter grows very littleeven as pressure is increased to 14-18 atmospheres. Such characteristicscan be drawbacks for postconditioning. Further, an angioplasty balloonis typically designed to open a stenosis or blood vessel along a lesion,rather than just occlude flow. Thus, the length of an angioplastyballoon is generally between 8 mm to 40 mm, while an occlusion ballooncould be shorter.

Another major drawback to using an angioplasty catheter forpostconditioning is that prior to use, the physician must measure theartery, for example, by fluoroscopy, then size the balloon both forlength and diameter, retrieve an appropriately sized balloon frominventory, and then go through various steps to prepare the balloon suchas removing the air trapped within the balloon before filling theballoon with saline/contrast mixture. Thus, using the angioplastycatheter with the angioplasty balloon suffers from inefficiencies.Further, the angioplasty catheter typically must be manually actuated toboth inflate and deflate the balloon. For example, the use of anangioplasty catheter for postconditioning usually requires rapidrotation of a screw piston in order to deliver the fluid in a controlledmanner, while watching the pressure gage of an Indeflator. Inflation ofthe balloon to a circular size can require 10-20 twists of theIndeflator in order to expand the balloon. During deflation, theIndeflator is normally directly unlocked and rapidly deflated. If acontrolled deflation is required, then the Indeflator can be manuallyscrewed down to a lower pressure. Physician to physician variabilitywill directly ensue, meaning that over the course of multiple inflationsand deflations, there will be a great variability in the rise and fallof blood flow in the artery. Normalizing the blood flow, i.e. the rateof inflation, pressure of inflation, and rate of deflation acrossphysicians can be critical to the efficacy of postconditioning. Inaddition to the cumbersome nature of actuating inflation and deflationof the angioplasty catheter, the speed of inflation is limited by thephysical capability or limitations of the treating physician to rapidlyrotate the screw piston. Given that many sequential inflations anddeflations are needed during a postconditioning, use of an angioplastycatheter has many drawbacks. As a result much time is lost in theprocess of using a conventional angioplasty catheter forpostconditioning.

Use of a conventional angioplasty catheter can also result insignificant operator-to-operator variability in inflation time, pressureof balloon, size of balloon, and deflation time. A system whichnormalizes the inflation time, pressure, size and deflation time isrequired, while still allowing operator control of the duration ofinflation. Lastly, angioplasty balloons, especially rapid exchangeballoons, do not have any means to deliver drug distal to the balloonwithout the added steps of removing the rapid exchange guidewire andreplacing the rapid exchange guidewire with an over-the-wire guidewire.

Therefore, a need exists for a system that is capable of restoring bloodflow after an ischemic event in an intermittent and gradual fashion withease and efficiency, while allowing the option of drug delivery distalto the balloon over a standard length guidewire. Further, there remainsa need for a pre-assembled kit for administering ischemicpostconditioning comprising a catheter and a handle having a fluidcircuit to control and modulate flow of inflation fluid to and from aballoon wherein the catheter is free from additional assembly andpreparation procedures such that it is ready-to-use within a variety ofvessel sizes. A need also exists for a fool-proof balloon catheter forangioplasty techniques, as described below. The disclosed subject matterincludes a method and apparatus for performing ischemic postconditioningin a much shorter time and at significantly reduced risk to the patientthan is possible with prior art technology.

Additionally, as mentioned above, PCTA is employed to dilate theischemic blockage and to restore the blood supply to the tissues andorgans when a patient suffers from an obstructed blood vessel, typicallyas a result of atherosclerosis. During PCTA, an empty (deflated) andcollapsed balloon disposed on a catheter is usually passed into thenarrowed location of the blood vessel and then inflated to a fixed size.Inflation of the balloon at the narrowed location of the blood vesselcompresses the obstruction to open up the blood vessel for improvedflow. During the angioplasty procedure, the physician is required todetermine whether the balloon is inflated by reviewing the balloon on amonitor or screen usually away from the patient undergoing thetreatment. Thus, the physician must be careful enough to maintain thecatheter at the lesion and take his view away from the patient to viewthe screen to make the determination if the balloon is inflated ordepend on another to view the monitor. Thus, there is a need for an easyto use balloon catheter having an indicator to indicate to the physicianwhen the balloon is inflated in a manner assures the physician theballoon is inflated without being required to turn away from the patientor make the judgment from a monitor.

SUMMARY OF INVENTION

The purpose and advantages of the present invention will be set forth inand apparent from the description that follows, as well as will belearned by practice of the present invention. Additional advantages ofthe present invention will be realized and attained by the methods andsystems particularly pointed out in the written description and claimshereof, as well as from the appended drawings.

To achieve these and other advantages and in accordance with the purposeof the disclosed subject matter, as embodied and broadly described, thedisclosed subject matter includes a method of administering ischemicpostconditioning comprising providing a catheter, the catheter includingan expandable member, the catheter configured for use in a variety ofvessel sizes, the catheter configured to receive a guidewire ofpredetermined size. A pressure source is provided and coupled with thecatheter, with the expandable member disposed in fluid communicationwith the pressure source, wherein the catheter is free from additionalassembly and preparation procedures. The expandable member is positionedat a predetermined location within a vessel and inflated with aninflation fluid for a period of time, and thereafter deflated.

Additionally, a therapeutic agent can be delivered simultaneously withpostconditioning. Further, the catheter can be configured to receive arapid exchange guidewire during delivery of the therapeutic agent. Theexpandable member conforms to the vessel wall having a non-circularcross-section at a pressure of about ⅔ atmospheres, and is repeatedlyinflated for about 30 seconds with an inflation liquid, e.g., CO₂.

In accordance with another aspect of the invention, the catheter isconfigured as a single-piece device arranged in a a pre-assembled kitwherein the catheter and handle, which includes a fluid circuit incommunication with the expandable member, comprise a system ready-to-usewithin a variety of vessel sizes.

In accordance with another aspect of the invention, a catheter that iscapable of efficient inflation and deflation of an expandable member isprovided. The catheter includes a fluid circuit generally having firstand second tubes and a plurality of valves to modulate flow of inflationfluid to a balloon disposed on the catheter body. In some embodiments,the catheter further includes an indicator that is configured toindicate to the physician whether the balloon is inflated while theballoon is in vivo. The advantages of the catheter removes the necessityof the physician to turn to view the balloon from fluoroscopic screen todetermine whether the balloon is indeed inflated.

In one embodiment, the catheter is part of a system for reducing orpreventing reperfusion injury to a patient. In this regard, the balloonis preferably a compliant balloon having a length and compliance forsequential inflation and deflation to effectuate postconditioningtechniques, such as those described in U.S. Publication 2004/0255956 toVinten-Johansen et al., the contents of which are incorporated herein byreference thereto. However, the catheter is applicable for use withother applications, such as angioplasty, stent delivery, etc. In thisregard, the balloon need not be a compliant balloon or a balloon capableof sequential inflation and deflation. Instead, a typical angioplastyballoon can be employed, as would be known in the art.

In one embodiment, the catheter includes an elongate shaft having aproximal end, a distal end and a length therebetween. The elongate shaftincludes an inflation lumen and a guidewire lumen. An expandable memberis disposed at or near the distal end of the elongate shaft. Thecatheter further includes a fluid circuit. The fluid circuit modulatesinflation fluid flow to inflate and deflate the expandable member.

In some embodiments, at least a part of the fluid circuit is housed in ahandle at the proximal end of the elongate shaft. The catheter systemcan include a non-removable handle attached to the elongate shaft. Inthis regard, the catheter system can be a disposable unit with noassembly required prior to use. The handle can include an actuator toeffect inflation or deflation of the expandable member. In this manner,the actuator controls fluid flow through the fluid circuit of thecatheter. The actuator can have a first position to actuate inflationfluid flow to the expandable member, and/or a second position to actuatedeflation fluid flow from the expandable member. The first position caninclude a momentary direction. The second position can include adetentable direction. In some embodiments, the system contains no morethan one actuator to inflate and deflate the expandable member. Theactuator can be, for example, a switch, a button, or a lever. Theswitch, button, or lever or other actuator can be configured to preventoverinflation of the expandable member. In this manner, the actuatorprovides the user with a one-touch actuation capability, and further,the prevention of overinflation provides a “fool-proof” system.

In some embodiments, the system includes a safety member to preventinflation fluid flow. The safety member can be housed in the handle ofthe system. In this manner, the safety member prevents commencement ofinflation fluid flow through the circuit.

The fluid circuit provides, in some instances, a closed loop circuit.The fluid circuit for example can include a first reservoir to house theinflation fluid, and inflation fluid passageway, such as the inflationlumen, and a plurality of valves to control flow of the inflation fluidto a balloon. The fluid circuit includes a piercing member, such as alancing device to pierce or tap the first reservoir to release theinflation fluid. In some embodiments, the piercing member controllablytaps the first reservoir. In some embodiments, the system includes aregulator to control pressure from the inflation fluid once releasedfrom the reservoir to the actuator. In some embodiment, the regulator isa valve.

In some embodiments, the actuator controls inflation fluid flow from thehandle to an inflation lumen. The actuator can control inflation flowthrough the inflation lumen to the expandable member. A splitter can beemployed to send or modulate the inflation fluid to the inflation lumenof the catheter. A second splitter having pulse valve can be used toeffectuate a time controlled flow of inflation fluid to the inflationlumen. In some embodiments, the fluid circuit further includes a checkvalve to direct flow of inflation fluid from the pulse valve to theinflation lumen. In some embodiments, a connector valve connects adeflation tube having a lumen from the expandable member to the checkvalve. An indicator can be disposed at the deflation tube to provideinformation about inflation or deflation of the expandable member. Insome embodiments, the indicator is an air indicator. Thus, the airindicator senses air pressure from the inflation fluid in the deflationtube signaling that the inflation fluid reached the expandable memberand inflated the expandable member such that the inflation fluidcontinued in the circuit to the deflation fluid. The expandable memberis preferably a balloon. In some embodiments, such as those for treatingreperfusion injury the balloon is sequentially inflatable anddeflatable.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and are intended toprovide further explanation of the disclosed subject matter claimed.

The accompanying drawings, which are incorporated in and constitute partof this specification, are included to illustrate and provide a furtherunderstanding of the method and system of the disclosed subject matter.Together with the description, the drawings serve to explain theprinciples of the disclosed subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS

A detailed description of various aspects, features, and embodiments ofthe subject matter described herein is provided with reference to theaccompanying drawings, which are briefly described below. The drawingsare illustrative and are not necessarily drawn to scale, with somecomponents and features being exaggerated for clarity. The drawingsillustrate various aspects and features of the present subject matterand may illustrate one or more embodiment(s) or example(s) of thepresent subject matter in whole or in part.

FIGS. 1 and 1A are schematic illustrations of a postconditioning methodin accordance with one embodiment of the disclosed subject matter;

FIGS. 2A-2C are schematic views of the system in accordance with oneembodiment of the disclosed subject matter;

FIG. 3A-3E are schematic illustrations of the catheter shaft inaccordance with embodiments of the disclosed subject matter;

FIGS. 4A and 4B are perspective views of embodiments of balloons inaccordance with the disclosed subject matter;

FIGS. 5A and 5B are cross sectional views of some embodiments of thehandle in accordance of with the disclosed subject matter;

FIGS. 5C to 5R are perspective views of various embodiments of handlesin accordance with the disclosed subject matter;

FIGS. 6A to 6C are schematic illustrates of a pulse valve in accordancewith the disclosed subject matter;

FIG. 7 is an exploded view of fluid circuit in accordance with oneembodiment of the disclosed subject matter;

FIGS. 7A to 7T are perspective views of exemplary components of thefluid circuit of FIG. 8; and

FIGS. 8A to 8C are block diagrams illustrating the inflation fluid flowthrough the fluid circuit in accordance with one embodiment of thedisclosed subject matter.

FIGS. 9A to 9N are side views of some embodiments of an arming device inaccordance with the disclosed subject matter.

FIG. 10 is a graphical presentation of a comparison of physicianattention allocation, in accordance with the disclosed subject matter.

FIG. 11 is a graphical presentation of a comparison of inflation anddeflation times, in accordance with the disclosed subject matter.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

It is understood that the subject matter described herein is not limitedto particular embodiments described, as such may, of course, vary. It isalso understood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting, since the scope of the present subject matter is limited onlyby the appended claims. Where a range of values is provided, it isunderstood that each intervening value between the upper and lower limitof that range and any other stated or intervening value in that statedrange, is encompassed within the disclosed subject matter.

I. System Overview

In accordance with the invention, a system is configured to permitsequential, such as intermittent and repeated, inflation and deflationof an expandable member, such as a balloon. In some embodiments, thesequential inflation and deflation of the balloon is achieved bysingle-touch actuation. The term “single-touch” as used herein meansthat actuation of inflation and deflation of the expandable member canbe achieved by a single switch, single button, or other single point ofactuation. In this regard, the user simply presses or otherwise actuatesan actuator to inflate the balloon, and presses it again to actuatedeflation of the balloon. Thus, unlike the angioplasty catheter thatgenerally requires sizing, prepping, and inflating by rotation of ascrew on the indeflator, one embodiment of the present system availsitself of quick use without the need for preparation.

A step by step comparison shows that while an angioplasty ballooncatheter requires many steps to size, prep, remove air bubbles and usethe device, a catheter system in accordance with an embodiment of thepresent system is much more efficient, thereby providing a shorterprocedure time and reduced risk to the patient.

One Embodiment of the Steps Typical Angioplasty System System 1. Sizevessel proximal to lesion Get package containing system 2. Determinesize of balloon Open Box containing system needed 3. Get Box(s) UnwrapProduct 4. Look Up Compliance Chart Engage Pressure 5. Choose final sizeAdvance to target lesion over guidewire 6. Open box containing Flipswitch On (no purge angioplasty system required, no air bubbles ifcarbon dioxide fluid used) 7. Unwrap product Flip switch off 8. PurgeIndeflator Repeat steps 6 and 7 to sequentially inflate and deflate 9.Connect Balloon to Indeflator 10. Prep Balloon (1st time = 3 steps) 11.Prep Balloon (2nd time = 3 steps) 12. Confirm no air bubbles 13. Advanceto target lesion 14. Lock Indeflator 15. Twist handle while watchingdial until target pressure diameter curve is reached (about 8 atm) 16.After 30 seconds, unlock Indeflator 17. Pull vacuum 18. Repeat steps14-17, repeat prep balloon if bubbles seen

This reduction in the number of steps and procedure time betweenconventional angioplasty balloons and the present invention isheightened when a therapeutic agent is delivered through the catheter.That is, angioplasty balloons, especially rapid exchange balloons, donot have any means to deliver drug distal to the balloon without theadded steps of removing the rapid exchange guidewire and replacing therapid exchange guidewire with an over-the-wire guidewire. Accordingly,the present invention alleviates this requirement and instead candeliver a therapeutic agent through the catheter while the catheter iscoupled with a rapid exchange guidewire.

The size and diameter of the balloon to be used in a conventionalangioplasty procedures is required to be matched to the size and nativediameter of the obstructed segment of the artery to be dilated. If theballoon size and diameter is smaller than the native artery, the resultsof balloon angioplasty are suboptimal, requiring a second dilation witha larger-sized balloon. In some cases, the result is a failed procedure,which may require either a second separate angioplasty procedure orbypass surgery. If the balloon is oversized in relation to theobstructed segment of the native vessel, the inner wall of the arterymay dissect from the remainder of the artery and may occlude the vesselcompletely, causing total cessation of blood flow to the target area ofthe myocardium. This complication can lead to acute myocardialinfarction and necessitate emergency bypass surgery. If the acuteocclusion leads to a large infarction, death is a possibility.

If a patient has a single obstruction in the right or left coronaryartery system, a single balloon catheter with a matching diameter andsize will be selected for the intended dilation procedure. When theballoon is inflated inside the obstructed segment of the native artery,the balloon should maintain the original preshaped configuration anddiameter under the maximum allowed pressure. In single lesion dilations,the choice of a properly-sized balloon catheter is relatively simple,although there are instances in which the original selection of theballoon catheter is inadequate so that a second balloon Catheter isnecessary to complete the procedure successfully.

However, in multi-vessel disease, balloon catheter selection becomescompounded and complex. For example, a patient may have three lesions inthe left coronary artery, and all three lesions may be approachableindividually for successful balloon angioplasty. But such lesions may bein vessels of different sizes. With conventional balloon catheters,angioplasty of these three differently-sized lesions is not alwaysimpossible, but it is cumbersome and inefficient. For each lesion, amatching balloon catheter is exchanged and manipulated into the targetlesion. To do this three times in a row requires roughly three times theprocedure time, three times the contrast amount, and a minimum of threeseparate balloon catheters and their accessory devices. Accordingly, thepresent invention provides a more efficient and effective ballooncatheter system designed as a pre-assembled device capable of deliverywithin a variety of vessel sizes, so as to provide a one-size-fits-alldevice for which the operator need not select a pressure or volume forinflation of the balloon.

In this regard, one embodiment of the system provides physicians with anefficient, easy to use catheter designed for rapid, sequential orrepeated inflation and deflation of a balloon, such as for reducing orpreventing reperfusion injury to an organ or tissue after an ischemicevent in the context of preventing or reducing reperfusion injury, orfor other applications. For applications in which the system is employedfor postconditioning applications, the system can be employed to (1)stop perfusion to the organ or tissue for an amount of time, and (2)permit perfusion to the organ or tissue for another period of time,repeating the stopping and perfusion steps sequentially, and (3) deliverbeneficial agents or contrast to areas distal to the balloon.

Beneficial agents include drugs, proteins, therapeutic agents, and otheragents that promote health or recovery. Some non-limiting examplesinclude calpain inhibitors, endothelin receptor blockers, pH stabilizingagents, antithrombotic agents, and proteins, cells or vectors includingangiogenic factors. Certain non-limiting calpain inhibitors and otherbeneficial agents are disclosed in WO 98/25899, WO 98/25883, WO 9954305,WO 99/54310, WO 99/61423, WO 00/78933, WO 2008/080969, WO 2009/083581,U.S. Publication Nos. 2006/0205671 and 2008/0097385, each of thedisclosures of which are incorporated herein by reference. Otherexamples of beneficial agents include nitroglycerin, epinepharin,lydocaine, heparin, hirudin, and ReoPro™. As will be recognized in theart, however, other drugs or beneficial agents may be employed.

In one embodiment, the catheter system as described herein is useful forpostconditioning methods. In this manner, the expandable member,preferably a balloon, is configured to occlude a blood vessel duringexpansion or inflation of the expandable member, and then permitresumption of perfusion of the blood flow during contraction ordeflation of an expandable member. The occluded vasculature can includea venous blood vessel as in retroperfusion, or an arterial blood vesselsuch as in reperfusion. The occluded blood vessels may be from thecoronary, peripheral, or cerebral vasculature. As illustrated in theschematic of FIG. 1, in one embodiment postconditioning is achieved byinflating and deflating the catheter balloon proximal to a lesion forone or more cycles of about 10 to 60 seconds. These cycles are repeatedas necessary to perform the postconditioning therapy. For example, anexpandable member is sequentially contracted and expanded such as topermit perfusion for about 10 to about 60 seconds and stop perfusion forabout 10 to about 60 seconds for a one or more cycles. In someembodiments, the cycles are repeated for about 3 to about 10 cycles. Asshown in FIG. 1, in one embodiment, the cycles for both inflation anddeflation are for a period of about 30 seconds each. Otherpostconditioning methods can be employed, however, such aspostconditioning methods described in U.S. Patent Publication No.2004/0255956 and 2007/0160645 to Vinten-Johansen et al., the disclosuresof which is incorporated herein by reference for all purposes. In someembodiments, the catheter is designed to postcondition a stented bloodvessel without changing the dimension of the implanted stent. In thismanner, the expandable member is a compliant balloon as described below,which does not negatively affect the implanted stent duringpostconditioning cycles of inflation and deflation of the balloon.

As illustrated in FIG. 1A, the postconditioning technique can beemployed prior to stenting a blood vessel or subsequent to stenting ablood vessel.

With regards to postconditioning prior to or after stenting, thepostconditioning device embodied herein will not dislodge the plaque.With regards to postconditioning after stenting, the postconditioningcan occur proximal to the stent, distal to the stent, and/or inside thestent. Advantageously, the catheter device embodied herein does notalter the shape or dimension of the deployed stent when postconditioningis employed within the stented vessel.

Accordingly, embodiments of the catheter of the invention can be usedfor postconditioning before or after placement of a stent in a bloodvessel.

As shown in FIG. 2A, the catheter system 10 generally includes acatheter having an elongate shaft 200, an expandable member 300 and afluid circuit including a control system 1000 (FIG. 2B) housed in ahandle (not shown). In some embodiments, handle 100 (FIG. 5A) isnon-removably attached to the catheter system such that a single unitarydevice is provided. Advantageously, the unitary device is packaged in aready-to-use state. In other words, the device can be a pre-assembledunit that is ready for use in any size vessel thereby eliminating theneed for measuring of the patient and selection of the appropriate sizeballoon and catheter, as is required in prior art devices. An exemplaryembodiment of the pre-assembled unit is illustrated in FIG. 2C. Once thedevice is removed from any packaging provided and coupled with theinflation fluid source, described in further detail below, the device isready for use. Further, in applications in which a therapeutic agent isdelivered, the device of the present invention provides for a moreefficient procedure in that a rapid exchange guidewire can remaindisposed within the lumen of the catheter during delivery of thetherapeutic agent. In some embodiments, expandable member 300 isdisposed at a distal section of the elongate shaft of the catheter.

The elongate shaft 200 includes at least two lumen, as better seen inFIGS. 3A to 3C. In one embodiment, the at least two lumen include aninflation lumen and a separate dedicated independent deflation lumen.Both the inflation lumen and the independent deflation lumen are influid communication with the interior portion of a balloon 300. In thisregard, an inflation fluid of any pressurized fluid, such as carbondioxide, noble gases including helium, neon, and pressurized liquidssuch as saline or contrast agents, is introduced into the balloon 300via the inflation lumen to inflate the balloon and then exits theballoon via the independent deflation lumen. The independent deflationlumen allows for rapid deflation of the balloon and in one embodiment isconfigured for Venturi-assisted deflation, as described below.

A handle 100 is disposed at or near the proximal end of the catheter andhouses the control system 1000 of the fluid circuit (FIGS. 5A and 5B).Handle 100 is configured to provide a physician with the ease ofautomatic, sequential inflation and deflation of expandable member 300by, in some embodiments, a one-touch actuator. In this manner, theone-touch actuator can be a switch, button, lever, or other deviceadapted to permit a user to inflate expandable member 300 when actuatedin a first position or direction, and to deflate expandable member 300when actuated in a second position or direction. The one-touch ease ofsequential inflation and deflation of expandable member 300 can beachieved by adapting the catheter shaft to include an independentinflation lumen and separate independent deflation lumen. In someembodiments, the switch is configured such that the user cannotoverinflate the expandable member 300. In this regard, the system caninclude a pulse valve that closes an outlet port to the expandablemember when the expandable member is fully inflated thereby preventingover inflation. In this manner, when the balloon is fully inflatedfurther actuation of the switch does not further inflate the balloon,thereby rendering the system “fool-proof” and effectuatingreproducibility with relation to inflation of the expandable member.

In some embodiments, the handle 100 includes a control system 1000 of afluid circuit disposed within the catheter device. The control system1000 is configured to assist modulation of inflation fluid flowthroughout the fluid circuit of the catheter system such as toeffectuate inflation and deflation of the expandable member 300. In someembodiments, the fluid circuit and in particular the independentdeflation lumen can be configured to induce a Venturi-assisted flow torapidly deflate expandable member 300, as will be described below.

II. The Catheter Body

In accordance with one embodiment, as shown FIG. 3A, the catheterincludes a generally elongate tubular shaft 200 having a proximal shaftsegment 201 and a distal shaft segment 202 in fluid communication.Proximal shaft segment 201 and distal shaft segment 202 can be formedfrom material having the same or similar hardness or durometer toprovide a uniform flexibility along the catheter body. Alternatively,the proximal shaft segment and distal shaft segment can be formed frommaterials having different flexibilities to provide a catheter having avaried flexibility along a length thereof. For example but notlimitation, the proximal shaft segment may be formed from a hypotube andthe distal shaft can be formed from a polymeric material to provideincreased flexibility along the catheter tubular shaft. As such, theproximal shaft and distal shaft segments can be formed from the sametube or alternatively can be two separate tubes connected or weldedtogether to form a unitary tube. The catheter may comprise one or morepolymers or polymer blends having different stiffness.

As illustrated in FIG. 3B, elongate shaft 200, in one embodiment,includes an independent inflation lumen 203 configured to provide apassage or flow of inflation fluid to an expandable member 300 disposedat or near the distal end 202 of the catheter shaft. Elongate shaft 200can also include an independent deflation lumen 204 to provide a secondfluid flow passage for the inflation fluid to outflow from expandablemember 300 during deflation. In this manner, the sequential inflationand deflation of expandable member 300, and consequential stopping andstarting of blood flow during postconditioning techniques can beefficient and rapid. For example, in one embodiment of the system, theexpandable member 300 can be inflated in five seconds or less,preferably one second or less, most preferably in 1/15th of a second orless. Further, the expandable member can be deflated in five seconds orless, and preferably three seconds or less, most preferably ¼ of asecond or less. This rapid inflation and deflation of the expandablemember provides advantages for postconditioning techniques not availablethrough use of the conventional angioplasty catheter.

The elongate shaft 200 can be formed in a number of shapes, for example,in one embodiment, the shaft can have a tubular configuration as shownin FIG. 3B. However, as would be known in the art other shapes can beemployed, such as elliptical.

The elongate shaft 200 can further include guidewire lumen 205, forexample, in addition to the inflation and deflation lumen. In thisregard, guidewire lumen 205 can be configured to extend from a tip 400at the distal end of elongate shaft 200 to a more proximal location ofthe elongate shaft 200 to provide an over-the-wire catheter.Alternatively, elongate shaft 200 may be formed to have a notch (notshown) disposed at a location between the distal end 202 and proximalend 201 of elongate shaft 200 to provide a rapid exchange catheter.

In accordance with another embodiment, elongate shaft 200 can furtherinclude a drug delivery lumen 206, such as for example, a drug infusionlumen configured to locally deliver beneficial agents such as thosedescribed above or other agents. In one embodiment, the beneficialagents are locally delivered to an area of a ischemic event. In otherembodiments, the catheter lacks a drug delivery lumen and instead, adrug coated balloon is disposed on the catheter shaft for local deliveryof a beneficial agent.

In some embodiments, the elongate shaft 200 includes four separate andindependent lumen (e.g., inflation lumen 203, deflation lumen 204,guidewire lumen 205, and drug delivery lumen 206). However, otherconfigurations can be employed. In some embodiments, the diameters ofthe lumen have different sizes. For example, in some embodiments, thedeflation lumen has a diameter of about twice the size of the inflationlumen diameter. In one embodiment, as depicted in FIG. 3C, the diameterof the inflation lumen 203 d is about 0.100 mm, the diameter of thedeflation lumen 204 d is about 0.200 mm, the diameter of the guidewirelumen 205 d is about 0.400 mm, and the diameter of the infusion lumen206 d is about 0.300 mm. Accordingly, each lumen can be configured tohave a different sized diameter, if desired.

In some embodiments, as illustrated in FIG. 3B, elongate shaft 200 canbe formed from a single extrusion with a plurality of lumen, e.g., thefour lumen as described above. As further shown, the four lumen can beoriented within the extrusion so that the extruded polymeric web 208remaining between the lumen forms an “I-beam” cross section. An I-beamconfiguration provides efficient form for resisting both bending andshear in the plane of the polymeric web 208. In this manner, theplurality of lumen 203, 204, 205, 206 are configured as independentlumen physically spaced from one another by polymeric web 208 disposedtherebetween. An advantage of the I-beam shape is that the cathetershaft is more resistant to bending when the catheter is pulled in aparticular direction.

In some embodiments, the different sized lumen are arranged or orientedwithin the extrusion to form a pattern such that the largest sized lumen205 is proximate each of the smaller sized lumen 203, 204, 206, asdepicted in FIGS. 3B and 3C, such that the polymeric web 208 disposedbetween the lumen 203, 204 and 205 forms the I-beam pattern, asillustrated in FIGS. 3D and 3E. In some embodiments, the thickness ofextruded polymeric web 208 is substantially equivalent to the bendingmoment of the shaft. A bending moment exists in a structural elementwhen a moment is applied to the element so that the element bends.Moments and torques are generally measured as a force multiplied by adistance so they have as unit newton-meters (N·m), or foot-pounds force(ft-lbf). In this manner, it is believed that the elongate shaft 200will resist bending equally, regardless of the direction of the bend tothe catheter shaft. It is further believed that a catheter shaft withoutthese features will bend to a different degree depending upon theorientation inside the vessel.

Elongate shaft 200 can further include a distal tip 400 (FIG. 3A) havinga proximal end abutting or overlapping the distal end 202 of thecatheter body. In one embodiment, catheter tip 400 includes one or morelumen. For example, in one embodiment, the tip 400 can include a firstlumen aligned with guidewire lumen 205 of elongate shaft 200, and asecond lumen aligned with infusion lumen 206. The guidewire lumen 205 isaligned with a lumen through the catheter tip 400 disposed at the distalend of the catheter shaft 202. These aligned lumens permit the catheterto ride over a guidewire. Furthermore, once properly inserted, theguidewire can be removed and fluid can be passed through the lumen.

In one embodiment, the tip 400 can be formed of a material softer thanthe material of the catheter such that the tip has sufficient columnstrength to resist buckling during insertion, but is sufficientlyflexible to deform when the tip is subjected to axial or radial loads inthe body in the absence of the guidewire. Catheter elongate shaft 200 isconfigured to enable the passage and the longitudinal translation ofguidewire within lumen 205 during a surgical procedure.

Elongate shaft 200 can be produced from a variety of materials,including metal, plastic and composite materials. In one embodiment,proximal shaft 201 is manufactured as a metal tube, for example, as astainless steel hypotube, and may be coated with a polymeric materialsuch as PTFE. The metal tube may also be covered with a single ormultilayered plastic material through one or more processes, includingcoextrusion, dipping, heat-shrinking, and electrostatic and thermalcoating. In another embodiment, elongate shaft 200 is manufactured as aplastic tube. Materials suitable for use in the catheter tube include,but are not limited to, Polyurethanes (PU), such as Tecoflex,Pellethene, Bionate, corethane, Elasteon, and blends thereof;Polyethylenes (PE), such as PET, PBT, PVDF, Teflon, ETFE, and blendsthereof, Polyolefins, such as HDPE, PE, LDPE, LLDPE, Polypropylene, andblends thereof, Polyimides; Polyamides; all classes of Nylons, such asNylon 11, Nylon 12, Nylon 6,6, Nylon 6, Nylon 7,11, Nylon 11,12, andblends thereof); block copolymers; PEBA-types polymers, such as ELY,PEBAX, Ubesta, and blends thereof, and biodegradable polymers.

Suitable materials also include blends of the above mentioned materialsas well as any composite materials, like dual-layers, tri-layers andmulti-layers thereof. For example, catheter shaft may be produced from atube comprising an outer layer made of Nylon and an inner layer made ofa lubricious material such as polyethylene or PTFE. A metallic ornonmetallic braiding may also be included within or between layers ofthe catheter shaft.

Catheter tip 400 can be configured to provide atraumatic contact betweenelongate shaft 200 and a wall against which elongate shaft 200 may bepushed during a surgical procedure. The catheter tip can be configuredas a soft tip, which in some embodiments, can be composed of a softsleeve that is affixed on and that extends beyond distal end 202, or,alternatively, that is affixed on and extends beyond the lumen ofelongate shaft 200. Typically, a soft tip is affixed through a weldingprocess, but other affixing techniques are also included within thescope of the present invention, for example, adhesive bonding. Suitablematerials for the sleeve can be chosen from any material suitable forproducing elongate shaft 200. The sleeve may be manufactured from amaterial softer than elongate shaft 200, and may be formed from the samematerial as expandable member 300 or from a different material, forexample, from any of the materials or combinations of materialsdescribed with reference to elongate shaft 200. In one embodiment, thesleeve is manufactured from a material having the same basic compositionas, but a lower Shore durometer hardness than, the expandable member 300material or the elongate tube 200 material. In another embodiment, thesleeve may be manufactured from a blend of PEBAX 55D and PEBAX 63Dpolymers. One skilled in the art will recognize that the sleeve may bemanufactured from a variety of other materials according to the previousdescription of materials, for example, a polyurethane, a polyethylene, apolyolefin, a polyimide, a polyamide like Nylon, a block copolymer, orblends, or compositions or dual layers or multi-layers thereof.

III. The Expandable Member

In accordance with one embodiment of the invention, expandable member300 is a polymeric balloon. Preferably, balloon 300 is a compliantballoon. Unlike a typical angioplasty balloon, which is configured toprovide a new circular, open lumen, the polymeric balloon 300 of theembodiment should be sufficiently compliant to mold to the anatomy ofthe blood vessel. In this manner, balloon 300 can occlude a blood vesselhaving a diameter from about 2 mm to about 30 mm depending on whetherthe application is for the coronary, cerebral or peripheral bloodvessels. In one embodiment, the balloon can occlude a blood vesselhaving a diameter from about 2 to about 4.5 mm for coronary or cerebralapplications, with a pressure of about 0.5 to 2 atm. For peripheralapplications, the balloon can occlude a blood vessel having a diameterfrom about 4 to about 30 mm, or any luminal orifice of the human bodywhere occlusion of fluid flow could be therapeutic.

In one embodiment, the balloon is a one-size-fits-all balloon. In thisregard, the balloon must be formed from a compliant polymeric material.For example and not limitation, the compliant balloon 300 can elongatewhen it is inflated within a narrow sized vessel, and can have aspherical shape when it inflated within a larger or wider blood vessel.Thus, the balloon is capable of molding to the blood vessel.Accordingly, the physician does not need to measure the artery of apatient prior to postconditioning to size balloon 300 to the patient.

In one embodiment, balloon 300 is mounted to elongate shaft 200 of thecatheter. Balloon 300 contains a hollow interior portion defining aninflation passage extending longitudinally therethrough to receiveinflation fluid from inflation lumen 203 of elongate shaft 200. In oneembodiment, the proximal portion of balloon 300 can be configured totaper radially inward at the proximal end and distal end of balloon 300.The proximal end and the distal end of balloon 300 are sized to mountand seal to respective portions of elongate shaft 200, while the ballooninterior portion is configured for selective inflation from anunexpanded first condition to an expanded second condition as shown inFIG. 4B. Hence, the transverse cross-sectional dimension of balloon 300,in the expanded condition, is significantly greater than that of theinwardly tapered end portions of proximal end and the distal end of theballoon.

When balloon 300 is mounted to elongate shaft 200, inflation lumen 203of elongate shaft 200 is in fluid communication with the inflationpassage of balloon 300. Accordingly, by operating the one-touch controlsystem at the proximal end of the catheter system, described below, theinterior portion of the expandable member 300 can be selectivelyinflated from the first condition to the inflated second condition.

Distal shaft 202 of the elongate shaft 200 extends through the inflationpassage of balloon 300, where a distal end of the catheter terminatesdistal to the distal end of the balloon 300. As best shown in FIG. 3A,distal shaft 202 extends longitudinally through the interior portion ofthe balloon 300, and defines the distal portion of the guidewire lumen205 where it terminates at a distal port at a distal end of the elongateshaft 200. Hence, a guidewire (not shown) may extend through guidewirelumen 205 of the elongate shaft 200, and out through the distal port ofthe catheter distal end. This passage enables the catheter to beadvanced along the guidewire that may be strategically disposed in avessel.

Balloon 300 can be formed in various shapes, as illustrated in FIGS. 4Aand 4B. As shown, the shape of balloon 300 can be spherical,cylindrical, or polygonal. Various polymers may be selected for theformation of balloon 300, as would be known in the art. However, theballoon material should be sufficiently compliant such that balloon 300can mold to the shape of the blood vessel.

In one embodiment, balloon 300 may be formed from a polyurethanematerial, such as TECOTHANE® (Thermedics). TECOTHANE® is athermoplastic, aromatic, polyether polyurethane synthesized frommethylene disocyanate (MDI), polytetramethylene ether glycol (PTMEG) and1,4 butanediol chain extender. TECOTHANE® grade 1065D is presentlypreferred, and has a Shore durometer of 65D, an elongation at break ofabout 300%, and a high tensile strength at yield of about 10,000 psi.However, other suitable grades may be used, including TECOTHANE® 1075D,having a Shore hardness of about D75. Other suitable compliant polymericmaterials include ENGAGE® (DuPont Dow Elastomers (an ethylenealpha-olefin polymer) and EXACT® (Exxon Chemical), both of which arethermoplastic polymers, elastomeric silicones, and latexes.

The compliant material may be crosslinked or uncrosslinked. Thepresently preferred polyurethane balloon materials are not crosslinked.By crosslinking the balloon compliant material, the final inflatedballoon size can be controlled.

Conventional crosslinking techniques can be used including thermaltreatment and E-beam exposure. After crosslinking, initialpressurization, expansion, and preshrinking, the balloon will thereafterexpand in a controlled manner to a reproducible diameter in response toa given inflation pressure.

In one embodiment, balloon 300 is formed from a low tensile set polymersuch as a silicone-polyurethane copolymer. Preferably, thesilicone-polyurethane is an ether urethane and more specifically analiphatic ether urethane such as PURSIL AL 575A and PURSIL AL10 (PolymerTechnology Group), and ELAST-EON 3-70A (Elastomedics), which aresilicone polyether urethane copolymers, and more specifically, aliphaticether urethane cosiloxanes.

In an alternative embodiment, the low tensile set polymer is a dienepolymer. A variety of suitable diene polymers can be used such as butnot limited to an isoprene such as an AB and ABApoly(styrene-block-isoprene), a neoprene, an AB and ABApoly(styrene-block-butadiene) such as styrene butadiene styrene (SBS)and styrene butadiene rubber (SBR), and 1,4-polybutadiene. The dienepolymer can be an isoprene including isoprene copolymers and isopreneblock copolymers such as poly(styrene-block-isoprene). A presentlypreferred isoprene is a styrene-isoprene-styrene block copolymer, suchas Kraton 1161K available from Kraton, Inc. However, a variety ofsuitable isoprenes can be used including HT 200 available from ApexMedical, Kraton R 310 available from Kraton, and isoprene (i.e.,2-methyl-1,3-butadiene) available from Dupont Elastomers. Neoprenegrades useful in the invention include HT 501 available from ApexMedical, and neoprene (i.e., polychloroprene) available from DupontElastomers, including Neoprene G, W, T and A types available from DupontElastomers.

In one embodiment, the polymeric material is a compliant material suchas, but not limited to, a polyamide/polyether block copolymer (commonlyreferred to as PEBA or polyether-block-amide). Preferably, the polyamideand polyether segments of the block copolymers may be linked throughamide or ester linkages. The polyamide block may be selected fromvarious aliphatic or aromatic polyamides known in the art. Preferably,the polyamide is aliphatic. Some non-limiting examples include nylon 12,nylon 11, nylon 9, nylon 6, nylon 6/12, nylon 6/11, nylon 6/9, and nylon6/6. Preferably, the polyamide is nylon 12. The polyether block may beselected from various polyethers known in the art. Some non-limitingexamples of polyether segments include poly(tetramethylene glycol),tetramethylene ether, polyethylene glycol, polypropylene glycol,poly(pentamethylene ether) and poly(hexamethylene ether). Commerciallyavailable PEBA material may also be utilized such as for example, PEBAX®materials supplied by Arkema (France). Various techniques for forming aballoon from polyamide/polyether block copolymer are known in the art.One such example is disclosed in U.S. Pat. No. 6,406,457 to Wang, thedisclosure of which is incorporated by reference.

In another embodiment, the balloon material is formed from polyamides.Preferably, the polyamide has substantial tensile strength, is resistantto pin-holing even after folding and unfolding, and is generally scratchresistant, such as those disclosed in U.S. Pat. No. 6,500,148 toPinchuk, the disclosure of which is incorporated herein by reference.Some non-limiting examples of polyamide materials suitable for theballoon include nylon 12, nylon 11, nylon 9, nylon 69 and nylon 66.Preferably, the polyamide is nylon 12. In yet another embodiment,balloon 300 is composed of several different layers, each one being adifferent polyamide or polyamide/polyether block copolymer.

In accordance with some embodiments, balloon 300 can be composed of asingle polymeric layer, or alternatively, can be a multilayered balloon,such as those described in U.S. Pat. No. 5,478,320 to Ishida, U.S. Pat.No. 5,879,369 to Trotta, or U.S. Pat. No. 6,620,127 to Lee, thedisclosures of which are incorporated herein by reference.

IV. The Handle and Fluid Circuit

As described above, the catheter system includes a handle 100 generallydisposed at or near the proximal end of the catheter. Handle 110 caninclude a housing of various shapes and configurations, as shown inFIGS. 5C to 5R. In one embodiment, handle 100 is non-removably attachedto the catheter such that the system is a unitary device requiringassembly prior to use. In other words, the catheter system can be soldin a “ready-to-use” state, unlike conventional angioplasty catheters asdescribed above.

The fluid circuit generally includes the inflation and independentdeflation lumen disposed along the catheter shaft 200, a control systemdisposed in the handle 100 and a plurality of valves to control andregulate pulsated and/or modulated flow of inflation fluid through thecatheter system.

In some embodiments, elongate shaft 200 includes an inlet port and anoutlet port. The inlet port is pressurized by a flow of inflation fluidfrom a first reservoir as part of the control system 1000 of the fluidcircuit. The inflation fluid flows through inflation lumen 203 ofelongate shaft 200, enters the interior portion of the expandable member300 via an inlet port. The inflow of the inflation fluid into theinterior of expandable member 300 causes it to inflate and occlude theblood flow in the artery when disposed therein. An outlet port disposedon the elongate shaft 200 facilitates deflation of expandable member 300by providing an opening for the inflation fluid to flow from expandablemember 300 to deflation lumen 204 during deflation.

The outlet port is configured to facilitate Venturi-assisted flow indeflation lumen 204 to deflate expandable member 300. For example,inflation lumen 203 and deflation lumen 204 can both be open withinexpandable member 300. The inflation fluid can pass from inflation lumen203, through expandable member 300, into deflation lumen 204. Inflationlumen 203 and the deflation lumen 204 are connected by a series ofone-way check valves. In one embodiment, the inflation pressure causesthe deflation check valve to stay closed. The pressure buildup (FIG. 7;117, 112, and 109) on the back side of the check valve and pulse valvecreate a Venturi effect to promote rapid deflation. When the actuator ismanipulated to the deflate position, pressure on the back side of adeflation check valve is removed. Thus the check valve opens andexpandable member 300 can deflate. The rapid exhaustion of the inflationpressure creates a Venturi effect, i.e. it draws the balloon down, andpulls the inflation fluid along. Thus, in some embodiments, theexpandable member is deflated in less than one second, and in someembodiments, less than ¼ of a second.

In one embodiment, as depicted in FIG. 5A, the control system 1000includes an actuator 107 that is capable of actuating inflation anddeflation of expandable member 300 with the ease of a flip of a finger.Actuator 107 can be actuated to sequentially inflate and deflate aballoon for postconditioning applications or other applications. It hasbeen found that reperfusion injury can result from rapid opening of anartery after a period of ischemia or interrupted blood flow, as forexample but not limitation during a STEMI or other occlusion. One methodfor decreasing reperfusion injury is to sequentially start and stop theblood flow in the infracted artery for multiple cycles immediately afterreopening the initial flow from the STEMI or other blockage. The presentdisclosure provides physicians with a system designed to achieveefficient, rapid, reproducible postconditioning. Fluid circuit 110,including control system 1000, is designed to allow operation of thesystem by a single actuator 107 with no other input or electronicsrequired referred to as “one-touch.” Actuator 107 can be configured toinclude a first position or direction for inflation and a secondposition or direction for deflation of expandable member 300. Forexample, the actuator 107 can be a button (FIG. 5F), a switch (FIG. 5A),or a lever (FIG. 5B), having a momentary direction to actuate inflationand a detentable direction to actuate deflation of the balloon. Bylimiting physician interaction to only one switch, button, or lever,reproducibility in inflating and deflating expandable member 300 inaccordance with the time requirements required for postconditioning canbe provided. Accordingly, the fluid circuit design and one-touchactuation provides ease of use for postconditioning, and provides a highdegree of reproducibility. Additionally, the device embodied hereinallows the physician administering postconditioning to focus on themonitor or other instrumentation, as opposed to necessarily focusing onthe device during use.

In one embodiment, the inflation fluid is released from the reservoir101 to regulator or a single pressure check valve, which controls thefluid pressure to the balloon 300. The regulated inflation fluid flowsthrough an inlet tubing 106 to the actuator 107, (e.g., switch) whichcontrols the flow of inflation fluid to the pulse valve 113 through acheck valve and then to balloon 115.

The pulse valve 113 allows inflation fluid to flow from an inlet port toan outlet port within the valve for a specified period of time. The timecan be specified, for example, by sizing the inlet port, outlet port,and opposing spring pressure inside the pulse valve, as described below.As best shown in FIGS. 6A to 6C, in one embodiment, the pulse valve 113includes an inner wall 1401 disposed within cylindrical body 1400.Cylindrical body 1400 has a first end 1410 and opposing second end 1411.An inner wall 1401 having an inlet port 1406 and an outlet port 1407 isdisposed within the body 1400 between first and second ends 1410 and1411. Preferably, the inlet port 1406 is larger than the outlet port1407 such that inflation fluid flows through the inlet port into thecylindrical body between the second end 1411 and inner wall 1401 at afaster rate than that which flows through the outlet port 1407 to thecylindrical body between the first wall 1410 and inner wall 1401.Accordingly, the amount of inflation fluid entering the inlet port 1406compared to the amount of inflation fluid exiting the outlet port 1406causes a buildup of fluid pressure between second wall 1411 and innerwall 1401. The buildup of pressure consequently applies a force to theinner wall and eventually overcomes the strength of spring 1402 andcauses the spring to compress, as shown in FIG. 6B as the inner wall ispushed from the pressure buildup. The inner wall 1401 contacts a stopmember 1405 disposed within the cylindrical body 1400. In someembodiments a stop is provided on the inner surface of the cylindricalbody. The stop is disposed proximate to an outlet port 115 which leadsto a pathway to expandable member, e.g., balloon 300 (not shown). Asshown in FIG. 6C, the inner wall 1401 contacts stop 1405 and becomesaxially aligned with outlet port 115 to balloon 300. When inner wall1401 is axially aligned with outlet port 115, the passageway provided bythe port is blocked so that no inflation fluid can travel to theexpandable member 300. Accordingly, the pulse valve 113 provides a“fool-proof” actuator. In this regard, the physician even if continuallydepressing the actuator to inflate the expandable member 300, cannotfurther inflate the expandable member because the outlet 115 is blockedby the inner wall 1401. Thus even if additional attempts at inflationare made, the system must de-energize before more inflation fluid isenabled to pass through the system. Thus, the system can safely controlthe amount of fluid entering an expandable member. The inflation fluidcan be various fluids known in the art. For example, the inflation fluidcan be a gas fluid or a liquid fluid. For the purpose of illustration,the inflation fluid can be carbon dioxide or saline.

In another embodiment, the fluid circuit includes a Venturi-assisteddeflation of the expandable member. In this manner, a vacuum is createdto rapidly deflate the inflation fluid from the expandable member. Inthis regard, when deflation is actuated by the physician, the pulsevalve is de-energized, the fluid inside the pulse valve escapes thusrelieving the pressure on the back side of a check valve, which createsa Venturi effect that decreases the time to deflate the balloon. In someembodiments, the expandable member deflates in less than about 5seconds, preferably in less than about 3 seconds.

As described herein, the fluid circuit 110 generally includes tubing 106and a plurality of check valves to modulate flow of the inflation fluidthrough the fluid circuit and eventually to the inflation lumen ofelongate shaft 200, which is in communication with fluid circuit 110 andexpandable member 300 and back through an independent deflation lumen.An exploded view of one embodiment of the fluid circuit is illustratedin FIG. 7. Fluid circuit 110 housed in the handle 100, can include thefollowing component parts: first reservoir 101 to provide high pressureinflation fluid, such as but not limited to a BestWhip (LG) (GenuineInnovations, Part 2042 or 4130) (FIG. 7A); a piercing mechanism 103 tocontrollably tap the first reservoir 101, such as lance assembly, e.g.,SA00102, SA00068, SA00101, or MM235008-21N, MM235008-11N (GenuineInnovations) (FIGS. 7B-7F, respectively); pressure regulator 104 (e.g.,MAR-1 (Clippard) or SA00196 (Genuine Innovations), FIGS. 7G-7H,respectively) to control pressure from inflation fluid to expandablemember 300. Alternatively, a single pressure check valve or anon-variable pressure regulator can be used such as for example,Qosina—P/N 11582 or “Lee Chek” Part Number CCPI2510014S, (FIG. 7P);connector 105 (not shown) to connect the pressure regulator 104 totubular member 106, e.g., UTO-2-PKG (Clippard) (FIG. 71); actuator 107to control the flow of inflation fluid from first reservoir 101 intoexpandable member 300; e.g., a main switch such as FBV-3DMF (Clippard)(FIG. 7K); connector 108 to connect tubular member 106 from pressureregulator 104 to actuator 107, e.g., CT2-PKG (Clippard) (FIG. 7J); flowsplitter 109 to split the flow of inflation fluid, e.g., UT0-2002-PKG(Clippard) (FIG. 7L); connector 111, such as, e.g., the CT2-PKG(Clippard) (FIG. 7M), to connect flow splitter 109 to pulse valve 113,such as, e.g., PV-1 (Clippard) (FIG. 7N), through tubular member 112 todeliver a volume of controlled pulse of inflation fluid to expandablemember 300; a connector 114, such as a rotational connector, e.g.,UTO-2-PKG (Clippard) (FIG. 7O), to connect pulse valve 113 to a one-waycheck valve 115 (e.g., CCPI2510000S (Lee Company) or Qosina—P/N 11582(FIG. 7P) that permits flow of inflation fluid to expandable member andensures the flow direction of the inflation fluid is one-way only, i.e.,from pulse valve 113 to inflation lumen 203 of elongate shaft 200; flowsplitter 116, such as, e.g., UT0-2002-PKG (Clippard) (FIG. 7R) which isconnected to flow splitter 109 through tubular member 117, wherein flowsplitter 109 connects the hose from deflation lumen 204 to pressureindicator 118; pressure indicator 118, such as, e.g., IND-1-WH(Clippard) (FIG. 7S), for showing that there is pressure in deflationlumen 204 to ensure expandable member 200 is inflated; double hose barb119 (not shown), such as C22-PKG (Clippard) (FIG. 7Q), for connectingcheck valve 120 to the hose going to the catheter; and check valve 120,such as CCP112510000S (Lee Company) (FIG. 7T), to ensure the flowdirection of inflation fluid from the outlet lumen on the catheter pulsevalve to inlet lumen 203.

As illustrated in the block diagram of FIG. 8A, in operation theinflation fluid, in this example carbon dioxide, flows out from storagein the first reservoir 101 by a piercing mechanism 103. The inflationfluid flows into a main valve or actuator switch. In some embodiments,the flow of inflation fluid is stopped into and out of the main valve.As shown in FIG. 8B, the fluid circuit can be configured to allow theinflation fluid to flow across the valve into a second check valve. Thegas is allowed to flow, in some embodiments, for about 0.1 seconds.After that time, the second valve can be configured to no longer allowflow of the inflation fluid. The check valve allows flow of theinflation fluid into the balloon but not out of the balloon. A thirdcheck valve allows inflation fluid flow out of the balloon, but not intothe balloon. The inflation fluid, such as the carbon dioxide gas, has ahigher pressure when it flows to the inflation check valve, so thesystem is locked (inflated) at this time. Further, as depicted in FIG.8C, the pressure inside the second valve exhausts, thereby creating aVenturi force, as noted above, which pulls the balloon into a deflatedposition as all the gas exhausts out from the top of the main valve. Themain valve does not allow gas to flow in at this time. Accordingly, thefluid circuit permits the user to sequentially inflate and deflate theexpandable member with the ease of rapid succession. The handle mayfurther include a pulse valve to deliver time-controlled, orvolume-controlled flow to the balloon 300. In this regard, the secondtubular member may include a one-way check valve to lock the pulse valvedelivered carbon dioxide in the expandable member 300.

V. Indicator

Deflation lumen, in some embodiments, includes an indicator, such as butnot limited to a pressure monitor, which ensures balloon is inflated. Insome embodiments the pressure monitor is disposed in-between the balloonand a deflation check valve to ensure the balloon is inflated. Forexample, if the catheter is kinked and not allowing inflation, then theindicator will not indicate inflated. Additionally, if the catheter hasa leak at the balloon, then the indicator will not indicate inflated.Accordingly, the indicator is a true test of balloon inflation.

In one embodiment, the indicator 118 (FIGS. 5A, 7) or a pressure markeris disposed at a proximal end of the system. In one embodiment, theindicator 118 includes a projection member associated with the deflationlumen of the system. In some embodiments, the indicator 118 isconfigured to extend at least partially through handle 100 when pressureis sensed in the deflation lumen of the system. In this manner, theindicator orientation can inform the physician of the state of theexpandable member. In other words, when the indicator extends from thehandle housing 100 and is visible to the physician due to, for example,pressure, forcing the button to extend then the physician is cognizantof the fact that inflation fluid is in the expandable member.Conversely, non-extension of the indicator from the handle 100 informsthe user that the expandable member is not fully inflated. As theindicator is in associated, such as for example, coupled, to thedeflation lumen at the proximal end of the system, the indicator cannotindicate or extend until pressure from the inflation fluid has flowedthrough the inflation lumen, made fluid communication with theexpandable member, and returned through the deflation lumen to theproximal section of the system. Thus, indicator 118 cannot indicatepressure unless the expandable member is inflated at the distal sectionof the catheter system. Advantageously, the indicator is an indicationof the true pressure inside the balloon. Conversely, an indicator whichis not in direct fluid communication with a deflation lumen will nottruly indicate if the balloon is inflated or deflated.

VI. Arming The Device

In one embodiment, as shown in the cross sectional views of FIGS. 5A and5B and best seen in FIG. 7, the control system 1000 of fluid circuit 110generally includes a first reservoir 101, such as a container orcanister, having stored inflation fluid. The first reservoir 101 can beselected (based on size) to inflate and deflate particular balloons ofspecified sizes. Accordingly, the size of the reservoir selected canprevent reuse and/or promote safety, especially when the inflation fluidis a pressurized gas such as carbon dioxide.

In some embodiments, an arming device 114 (FIG. 9A) is disposed proximalto the first reservoir and is configured to arm the device. The armingdevice can be non-reversible. In this regard, “non-reversible” meansthat once the device is armed, it cannot be disarmed. The arming device114 is actuated by the physician prior to use in order to pierce thereservoir 110 which contains the inflation fluid. For example, asdepicted in FIGS. 9A and 9B, when arming device 114 is pushed down,first reservoir 101 is pushed forward and a ratchet located on handlehousing 112 engages tab 116, thus preventing arming device 114 fromreturning to its original position. The system is armed, therebyallowing the fluid to flow from an opening in first reservoir 101.

Further embodiments of arming device 114 are depicted in FIGS. 9C-9N.For example, in FIGS. 6C and 6D, arming device 114 is formed from button114 a and wedge 114 b which are positioned such that a downward force onbutton 114 a causes wedge 114 b to move in a perpendicular direction,thereby advancing first reservoir 101 forward into an armed position byreleasing inflation fluid stored in the reservoir 101. Tab 116 againengages a ratchet located on handle housing 112, preventing both button114 a and wedge 114 b from returning to their original positions.

Lever type safeties 114 are depicted in FIGS. 9E to 9J. As shown, thephysician must move the lever from a first position to a second positionin order to advance first reservoir 101 into its armed position. Theinitial and final position of lever arming device 114 depend solely onthe manufacturing requirements of the system. In some embodiments, aratchet located on the side of handle housing 112 engages the sides oflever arming device 114, thereby preventing lever arming device 114 fromreturning to its original position.

A pull tab type arming device 114, as shown in FIGS. 9K-9L, may also beutilized in accordance with some embodiments of the invention. In suchembodiments, pull tab type arming device may be formed from pull tab 114c and spring mechanism 114 d. The spring is biased in a contracted stateuntil the pull tab is removed. By removing pull tab 114 c from handle100, spring mechanism 114 d is allowed to expand such that the springapplies a force that pushes or otherwise allows first reservoir 101 toengage a tapping device such as a lancet to arm the device.

In other embodiments, arming device 114 may be a screw type armingdevice, as depicted in FIGS. 9M-9N. As shown, threads 114 e, located onarming device 114, engage an opening in housing 112. Rotating armingdevice 114 in the appropriate direction causes arming device 114 toadvance forward and advance first reservoir 101 into its armed position.In some embodiments, arming device 114 may contain a locking mechanism(not shown) that prevents first reservoir 101 from being disarmed and/orrotating in the wrong direction.

As described the arming device 114 arms the first reservoir 101 bycausing engagement of the first reservoir 101 with piercing member 103(FIGS. 5B, 7) so that the reservoir is tapped or pierced to release theinflation fluid contained in the reservoir housing. The outflow ofinflation fluid enters the fluid circuit and eventually flows to theexpandable member at the distal section of the catheter body and outfrom the balloon via an independent deflation lumen.

VII. Testing of the Presently Disclosed System

A study of the device and method of the present disclosure was conductedin comparison to a conventional angioplasty catheter, and a controlgroup in which no reperfusion was conducted. A total occlusion wasestablished in an artery to simulate an ischemic event, after whichcomparisons were made between the control group (i.e. nopostconditioning), postconditioning via conventional angioplastycatheters, and postconditioning via the presently disclosed techniqueand apparatus.

FIG. 10 illustrates a comparison between the three different sample setstested. In accordance with an aspect of the disclosed subject matter,and as discussed above, the method and apparatus disclosed hereinreduces the amount of steps required for the postconditioning procedure.The reduction in steps, and corresponding reduction in time required toconduct postconditioning allows the physician, or otherinterventionalist, to focus more of their attention and care on thepatient, rather than be preoccupied with an array of steps and devicecomponents as required with conventional angioplasty catheters.Particularly, and as shown in FIG. 10, the operator of the device of thepresent disclosure spends 97.5% of the procedure time focused on thepatient. This is over a 17% increase over conventional angioplastycatheter procedures.

Accordingly, the “PUFF” device disclosed herein requires less proceduralsteps, and provides a pre-assembled device with a trigger operationwhich results in a greater amount of physician/interventionalist focuson the patient. In one experiment, over 8 cycles of 30-secondPostconditioning (8×30 sec inflated, 8×30 sec deflated) were performedtotaling 480 seconds. The device of the present disclosure allows theoperator to focus 468 seconds on the patient (12 seconds looking awayfrom the monitors), while a conventional Angioplasty-Indeflator deviceallows the operator to focus 428 total seconds (52 seconds looking awayfrom the monitor and other important instruments during the care of apatient. Moreover, the apparatus of the present disclosure can beoperated by a single physician/interventionalist whereas conventionalover-the-wire angioplasty devices may require two physicians to operatedue (to the need to remove the guidewire during delivery of fluids.)

In accordance with another aspect of the present disclosure, theinflation and deflation of the balloon can be controlled via a triggeror button as described above. This is advantageous in that it allows forrapid occlusion and deocclusion, and thus shorter reperfusion cycletimes. FIG. 12 illustrates a comparison of the inflation and deflationtimes for the apparatus of the present disclosure (“PUFF”) and aconventional angioplasty device (“AngioPC”). As depicted, the apparatusof the present disclosure greatly reduces the time required to bothinflate and deflate the balloon, wherein the time to deflate is the timerequired to restore visible perfusion to the artery, as seen by contrastflow within the lumen.

While the disclosed subject matter is described herein in terms ofcertain preferred embodiments, those skilled in the art will recognizethat various modifications and improvements may be made to the disclosedsubject matter without departing from the scope thereof. Moreover,although individual features of one embodiment of the disclosed subjectmatter may be discussed herein or shown in the drawings of the oneembodiment and not in other embodiments, it should be apparent thatindividual features of one embodiment may be combined with one or morefeatures of another embodiment or features from a plurality ofembodiments.

In addition to the specific embodiments claimed below, the disclosedsubject matter is also directed to other embodiments having any otherpossible combination of the dependent features claimed below and thosedisclosed above. As such, the particular features presented in thedependent claims and disclosed above can be combined with each other inother manners within the scope of the disclosed subject matter such thatthe disclosed subject matter should be recognized as also specificallydirected to other embodiments having any other possible combinations.Thus, the foregoing description of specific embodiments of the disclosedsubject matter has been presented for purposes of illustration anddescription. It is not intended to be exhaustive or to limit thedisclosed subject matter to those embodiments disclosed.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the method and system of thedisclosed subject matter without departing from the spirit or scope ofthe disclosed subject matter. Thus, it is intended that the disclosedsubject matter include modifications and variations that are within thescope of the appended claims and their equivalents.

What is claimed is:
 1. A method of administering ischemicpostconditioning comprising: providing a catheter, the catheterincluding at least one expandable member, the catheter configured foruse in a variety of vessel sizes, the catheter configured to receive aguidewire of predetermined size; providing a handle having a pressuresource positioned entirely within the handle; coupling the pressuresource with the catheter, the at least one expandable member disposed influid communication with the pressure source, wherein the catheter andhandle are free from any required additional assembly and preparationprocedures; positioning the at least one expandable member at apredetermined location within a vessel; inflating the at least oneexpandable member with an inflation fluid via an inflation lumen for aperiod of time; and deflating the at least one expandable member via anindependent deflation lumen.
 2. The method of claim 1, wherein atherapeutic agent is delivered simultaneously with postconditioning. 3.The method of claim 2, wherein the catheter is configured to receive arapid exchange guidewire during delivery of the therapeutic agent. 4.The method of claim 1, wherein the expandable member conforms to thevessel wall at a pressure of about ⅔ atm.
 5. The method of claim 1,wherein the expandable member is inflated for about 30 seconds.
 6. Themethod of claim 1, wherein the inflation fluid is CO₂.
 7. The method ofclaim 1, wherein the inflation of the at least one expandable member isrepeated.
 8. The method of claim 1, wherein the catheter is configuredto receive a rapid exchange guidewire.
 9. The method of claim 1, whereinthe expandable member is a balloon.
 10. The method of claim 1, whereinthe expandable member is configured to conform to a lumen wall having anon-circular cross-section.
 11. A method of administering ischemicpostconditioning comprising: providing a catheter, the catheterincluding at least one expandable member, the catheter configured foruse in a variety of vessel sizes, the catheter configured to receive aguidewire of predetermined size; providing a handle having a pressuresource positioned entirely within the handle; coupling the pressuresource with the catheter, the at least on expandable member disposed influid communication with the pressure source; positioning the at leastone expandable member at a predetermined location within a vessel;inflating the at least one expandable member with an inflation fluid viaan inflation lumen for a period of time; delivering a therapeutic agentto a predetermined location within the vessel; and deflating the atleast one expandable member via an independent deflation lumen.
 12. Themethod of claim 11, wherein the catheter is configured as a single-piecedevice.
 13. The method of claim 11, wherein the catheter is configuredto receive a rapid exchange guidewire during delivery of the therapeuticagent.
 14. The method of claim 11, wherein the expandable memberconforms to the vessel wall at a pressure of about ⅔ atm.
 15. The methodof claim 11, wherein the expandable member is inflated for about 30seconds.
 16. The method of claim 11, wherein the inflation fluid is CO₂.17. The method of claim 11, wherein the inflating of the at least oneexpandable member is repeated.
 18. The method of claim 11, wherein theexpandable member is a balloon.
 19. The method of claim 11, wherein theexpandable member is configured to conform to a lumen wall having anon-circular cross-section.
 20. A pre-assembled kit for administeringischemic postconditioning comprising: a catheter, the catheter having atleast one lumen extending therethrough, the catheter having at least oneexpandable member; and a handle, the handle including a pressure sourcepositioned entirely within the handle and a fluid circuit defining atleast an inflation lumen and an independent deflation lumen, the fluidcircuit in communication with the at least one expandable member;wherein the catheter system ready-to-use within a variety of vesselsizes.
 21. The preassembled kit of claim 20, wherein the catheter andhandle are a unitary device.
 22. The preassembled kit of claim 21,wherein the pre-assembled kit includes an expandable member that isinflated with one touch.
 23. The preassembled kit of claim 22, whereinthe expandable member is configured such that no purge is necessaryprior to use.
 24. The pre-assembled kit of claim 20, wherein theexpandable member is a one-size-fits-all balloon.
 25. The pre-assembledkit of claim 24, wherein a size of the expandable member need not bechosen by a health care provider using the kit such that the kit isready to use.